Genetic Variant NM_016272.4:c.789C>T (chr22-41436557-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016272.4(TOB2):c.789C>T(p.Asn263Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00488 in 1,609,368 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 87 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 119 hom. )

Consequence

TOB2
NM_016272.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.43

Publications

3 publications found

Variant links:

Genes affected

TOB2 (HGNC:11980): (transducer of ERBB2, 2) TOB2 belongs to the TOB (see TOB1; MIM 605523)/BTG1 (MIM 109580) family of antiproliferative proteins, which are involved in the regulation of cell cycle progression.[supplied by OMIM, Apr 2004]

TOB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 22-41436557-G-A is Benign according to our data. Variant chr22-41436557-G-A is described in ClinVar as Benign. ClinVar VariationId is 784421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016272.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOB2	NM_016272.4	MANE Select	c.789C>T	p.Asn263Asn	synonymous	Exon 2 of 2	NP_057356.1	Q14106-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOB2	ENST00000327492.4	TSL:1 MANE Select	c.789C>T	p.Asn263Asn	synonymous	Exon 2 of 2	ENSP00000331305.3	Q14106-1
TOB2	ENST00000434408.2	TSL:2	c.789C>T	p.Asn263Asn	synonymous	Exon 2 of 2	ENSP00000388549.2	Q14106-1
TOB2	ENST00000901391.1		c.789C>T	p.Asn263Asn	synonymous	Exon 2 of 2	ENSP00000571450.1

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2913

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0605

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00154

Gnomad OTH

AF:

0.0234

GnomAD2 exomes

AF:

0.00652

AC:

1540

AN:

236278

AF XY:

0.00531

show subpopulations

Gnomad AFR exome

AF:

0.0595

Gnomad AMR exome

AF:

0.00556

Gnomad ASJ exome

AF:

0.0182

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000593

Gnomad NFE exome

AF:

0.00187

Gnomad OTH exome

AF:

0.00564

GnomAD4 exome

AF:

0.00338

AC:

4928

AN:

1457008

Hom.:

119

Cov.:

AF XY:

0.00321

AC XY:

2324

AN XY:

724502

show subpopulations

African (AFR)

AF:

0.0696

AC:

2327

AN:

33424

American (AMR)

AF:

0.00638

AC:

277

AN:

43420

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

434

AN:

25996

East Asian (EAS)

AF:

0.00

AC:

AN:

39556

South Asian (SAS)

AF:

0.00148

AC:

127

AN:

85744

European-Finnish (FIN)

AF:

0.000715

AC:

AN:

53112

Middle Eastern (MID)

AF:

0.0279

AC:

161

AN:

5768

European-Non Finnish (NFE)

AF:

0.000968

AC:

1074

AN:

1109748

Other (OTH)

AF:

0.00813

AC:

490

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

329

658

987

1316

1645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0192

AC:

2918

AN:

152360

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

1353

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.0604

AC:

2511

AN:

41574

American (AMR)

AF:

0.0110

AC:

169

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00228

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00154

AC:

105

AN:

68042

Other (OTH)

AF:

0.0232

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

133

267

400

534

667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0100

Hom.:

Bravo

AF:

0.0218

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.86

(source)

DANN

Benign

0.51

PhyloP100

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over